INHIBITION OF TOOSENDANIN ON THE DELAYED RECTIFIER POTASSIUM CURRENT IN NEUROBLASTOMA X GLIOMA NG108-15 CELLS

The effect of Toosendanin (TSN), a presynaptic transmission blocker, o n the outward delayed rectifier potassium current (I-KD) of NG108-15 c ells was studied by using the whole-cell voltage-clamp technique. It w as observed that externally applying TSN not only reduced I-KD amplitu de in a dose-dependent and partial reversible manner but also accelera ted its inactivation. The effect of internally applying TSN was also e xamined by including TSN in the electrode, and it was the same as that of externally applying TSN. Further, comparison observations with TEA , 4-AP, verapamil, nifedipine, and(+/-)-Bay K 8644 were also made, and the results were as follows. The time courses of TSN's inhibition eff ect as well as its recovery after washing were much slower than those of TEA and 4-AP. Externally applying TEA or 4-AP reduced I-KD amplitud e but did not accelerate its inactivation. Externally applying verapam il, nifedipine, or (+/-)-Bay K 8644, however, similarly to the effect of TSN, not only reduced I, amplitude but also accelerated its inactiv ation. Thus, from the obtained results it is suggested that TSN might diffuse into the cell interior and act intracellularly, and the underl ying mechanism might be different from that of TEA and 4-AP but simila r to that of verapamil, nifedipine, and (+/-)-Bay K 8644 to some exten t. (C) 1997 Elsevier Science B.V.